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Objective: To study socio-economic inequalities in patient-reported outcomes in primary hip and knee arthroplasty (THA/TKA) patients for osteoarthritis, using two analytical techniques., Methods: We obtained data from 44,732 THA and 30,756 TKA patients with preoperative and 12-month follow-up PROMs between 2014 and 2020 from the Dutch Arthroplasty Registry. A deprivation indicator based on neighborhood income, unemployment rate, and education level was linked and categorized into quintiles. The primary outcome measures were the EQ-5D-3L index and Oxford Hip/Knee Score (OHS/OKS) preoperative, at 12-month follow-up, and the calculated change score between these measurements. We contrasted the most and least deprived quintiles using multivariable linear regression, adjusting for patient characteristics. Concurrently, we calculated concentration indices as a non-arbitrary tool to quantify inequalities., Results: Compared to the least deprived, the most deprived THA patients had poorer preoperative (EQ-5D -0.03 (95%CI -0.02, -0.04), OHS -1.26 (-0.99, -1.52)) and 12-month follow-up health (EQ-5D -0.02 (-0.01, -0.02), OHS -0.42 (-0.19, -0.65)), yet higher mean change (EQ-5D 0.02 (0.01, 0.03), OHS 0.84 (0.52, 1.16)). The most deprived TKA patients had similar results. The higher mean change among the deprived resulted from lower preoperative health in this group (confounding). After accounting for this, the most deprived patients had a lower mean change. The concentration indices showed similar inequality effects and provided information on the magnitude of inequalities over the entire socio-economic range., Conclusion: The most deprived THA and TKA patients have worse preoperative health, which persisted after surgery. The concentration indices allow comparison of inequalities across different outcomes (e.g., revision risk)., Competing Interests: Declaration of Competing Interest JB, MR, JV, and MJ declare they had financial support from the EuroQol Research Foundation for the submitted work. LV and GB declare to have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We systematically reviewed the literature to identify comparative studies of core treatments (exercise, education, or weight management), adjunct treatments (e.g. electrotherapeutical modalities, bracing), or multimodal treatments (core plus other treatments), for treating osteoarthritis (OA) complaints, published between 1 March 2022 and 1 March 2023., Design: We searched three electronic databases for peer-reviewed comparative studies evaluating core treatments, adjunct treatments, or multimodal treatments for OA affecting any joint, in comparison to other OA treatments. Two authors independently screened records. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. A narrative synthesis focusing on pain and function outcomes was performed in studies with a mean sample size of at least 46 participants per treatment arm., Results: 33 publications (28 studies), 82% with PEDro ratings of good or excellent, were eligible for narrative synthesis: 23 studies evaluated knee OA; one knee OA or chronic low back pain; two knee or hip OA; one hip OA only; and one thumb OA. No studies identified a dose, duration or type of exercise that resulted in better pain or function outcomes. Core treatments generally showed modest benefits compared to no or minimal intervention controls., Conclusions: Rehabilitation research continues to be focused on the knee. Most studies are not adequately powered to assess pain efficacy. Further work is needed to better account for contextual effects, identify treatment responder characteristics, understand treatment mechanisms, and implement guideline care., Competing Interests: Declaration of Competing Interest EM Macri received travel support from Osteoarthritis Research Society International (OARSI) to present the findings of this study at the OARSI World Congress in Denver, USA in March 2023. Authors declare no other competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: The aim of this study was to evaluate the cost-effectiveness of arthroscopic partial meniscectomy versus physical therapy plus optional delayed arthroscopic partial meniscectomy in young patients aged under 45 years with traumatic meniscal tears., Methods: We conducted a multicentre, open-labelled, randomized controlled trial in patients aged 18 to 45 years, with a recent onset, traumatic, MRI-verified, isolated meniscal tear without knee osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with an optional delayed arthroscopic partial meniscectomy after three months of follow-up. We performed a cost-utility analysis on the randomization groups to compare both treatments over a 24-month follow-up period. Cost utility was calculated as incremental costs per quality-adjusted life year (QALY) gained of arthroscopic partial meniscectomy compared to physical therapy. Calculations were performed from a healthcare system perspective and a societal perspective., Results: A total of 100 patients were included: 49 were randomized to arthroscopic partial meniscectomy and 51 to physical therapy. In the physical therapy group, 21 patients (41%) received delayed arthroscopic partial meniscectomy during follow-up. Over 24 months, patients in the arthroscopic partial meniscectomy group had a mean 0.005 QALYs lower quality of life (95% confidence interval -0.13 to 0.14). The cost-utility ratio was €-160,000/QALY from the healthcare perspective and €-223,372/QALY from the societal perspective, indicating that arthroscopic partial meniscectomy incurs additional costs without any added health benefit., Conclusion: Arthroscopic partial meniscectomy is arthroscopic partial meniscectomy is unlikely to be cost-effective in treating young patients with isolated traumatic meniscal tears compared to physical therapy as a primary health intervention. Arthroscopic partial meniscectomy leads to a similar quality of life, but higher costs, compared to physical therapy plus optional delayed arthroscopic partial meniscectomy., Competing Interests: D. E. Meuffels and M. A. Koopmanschap report an institutional grant from Zon MW, paid to Erasmus MC, related to this study., (© 2023 van der Graaff et al.)

Background: Traumatic knee injury results in a 4- to 10-fold increased risk of post-traumatic osteoarthritis (PTOA). Currently, there are no successful interventions for preventing PTOA after knee injury. The aim of this study is to identify inflammatory proteins that are increased in serum and synovial fluid after acute knee injury, excluding intra-articular fractures., Methods: A literature search was done according to the PRISMA guidelines. Articles reporting about inflammatory proteins after knee injury, except fractures, up to December 8, 2021 were collected. Inclusion criteria were as follows: patients younger than 45 years, no radiographic signs of knee osteoarthritis at baseline, and inflammatory protein measurement within 1 year after trauma. Risk of bias was assessed of the included studies. The level of evidence was determined by the Strength of Recommendation Taxonomy., Results: Ten studies were included. All included studies used a healthy control group or the contralateral knee as healthy control. Strong evidence for interleukin 6 (IL-6) and limited evidence for CCL4 show elevated concentrations of these proteins in synovial fluid (SF) after acute knee injury; no upregulation in SF for IL-2, IL-10, CCL3, CCL5, CCL11, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was found. Limited evidence was found for no difference in serum concentration of IL-1β, IL-6, IL-10, CCL2, and tumor necrosis factor alpha (TNF-α) after knee injury., Conclusion: Interleukin 6 and CCL4 are elevated in SF after acute knee injury. Included studies failed to demonstrate increased concentration of inflammatory proteins in SF samples taken 6 weeks after trauma. Future research should focus on SF inflammatory protein measurements taken less than 6 weeks after injury.

Background and purpose - Quantitative T2 mapping MRI of cartilage has proven value for the assessment of early osteoarthritis changes in research. We evaluated knee cartilage T2 relaxation times in a clinical population with knee complaints and its association with patients and disease characteristics and clinical symptoms.Patients and methods - In this cross-sectional study, T2 mapping knee scans of 109 patients with knee pain who were referred for an MRI by an orthopedic surgeon were collected. T2 relaxation times were calculated in 6 femoral and tibial regions of interest of full-thickness tibiofemoral cartilage. Its associations with age, sex, BMI, duration of complaints, disease onset (acute/chronic), and clinical symptoms were assessed with multivariate regression analysis. Subgroups were created of patients with abnormalities expected to cause predominantly medial or lateral tibiofemoral cartilage changes.Results - T2 relaxation times increased statistically significantly with higher age and BMI. In patients with expected medial cartilage damage, the medial femoral T2 values were significantly higher than the lateral; in patients with expected lateral cartilage damage the lateral tibial T2 values were significantly higher. A traumatic onset of knee complaints was associated with an acute elevation. No significant association was found with clinical symptoms.Interpretation - Our study demonstrates age, BMI, and type of injury-dependent T2 relaxation times and emphasizes the importance of acknowledging these variations when performing T2 mapping in a clinical population.

Aims: Meeting preoperative expectations is known to be of major influence on postoperative satisfaction after total knee arthroplasty (TKA). Improved management of expectation, resulting in more realistic expectations can potentially lead to higher postoperative satisfaction. The objective of this study was to assess the effect of an additional preoperative education module, addressing realistic expectations for long-term functional recovery, on postoperative satisfaction and expectation fulfilment., Methods: In total, 204 primary TKA patients with osteoarthritis were enrolled in this randomized controlled trial (RCT). Patients were allocated to either usual preoperative education (control group) or usual education plus an additional module on realistic expectations (intervention group). Primary outcome was being very satisfied (numerical rating scale for satisfaction ≥ 8) with the treatment result at 12 months' follow-up. Other outcomes were change in preoperative expectations and postoperative expectation fulfilment., Results: A total of 187 patients (91.7%) were available for analysis at follow-up. In the intention-to-treat analysis, 58.5% (55/94) of patients were very satisfied with the treatment result in the control group, and 69.9% (65/93) of patients in the intervention group (adjusted odds ratio (AOR) 1.72, 95% confidence interval (CI) 0.90 to 3.29). A per-protocol analysis for patients who attended the education session (92.0%, n = 172) showed that 56.9% (49/86) of patients were very satisfied in the control group and 74.4% (61/86) in the intervention group (AOR 2.44, 95% CI 1.21 to 4.91). After preoperative education, the expectation scores in the intervention group were significantly lower (mean difference -6.9 (95% CI -10.2 to -3.6)) and did not alter in the control group (mean difference 0.5 (95% CI -2.9 to 3.9)). Overall, fulfilment of expectations at 12 months was significantly higher in the intervention group (mean difference 11.4% (95% CI 2.3 to 20.5))., Conclusion: Improved preoperative patient education can modify patient expectations, resulting in higher postoperative fulfilment of expectation and higher satisfaction in the group that attended the preoperative education. This is the first RCT to confirm the potential of improved expectation management on satisfaction after TKA. Cite this article: Bone Joint J  2021;103-B(4):619-626.

Background: Physiotherapy is a proven effective treatment strategy after total knee and hip arthroplasty (TKA/THA), however there is considerable practice variation regarding its timing, content and duration. This study aims to compare the (cost-) effectiveness of a standardized, treat-to-target postoperative physiotherapy strategy with usual postoperative care., Methods: Using a cluster randomized study design, consecutive patients scheduled for a primary TKA/THA in 18 hospitals in the Netherlands will be assigned to the treat-to-target physio therapy strategy or usual postoperative care. With the treat-to-target strategy a standardized, individually tailored, exercise program is aimed at the attainment of specific functional milestones. Assessments are done at baseline, 6 weeks and 3, 6, 9 and 12 months follow up. The primary outcome will be the Knee injury / Hip disability and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS / HOOS-PS) at 3 months follow up. Secondary outcomes are the numeric rating scale for pain, the Oxford Knee and Hip Scores, performance-based test and the EuroQol 5D-5L for quality of life. Healthcare use, productivity and satisfaction with postoperative care are measured by means of questionnaires. In total, 624 patients will be needed of which 312 TKA and 312 THA patients., Discussion: The study will provide evidence concerning the (cost-) effectiveness of the treat-to-target postoperative physiotherapy treatment compared to usual postoperative care. The results of this study will address an important evidence gap and will have a significant impact in daily practice of the physio therapist., Trial Registration: Registered in the Dutch Trial Registry on April 15, 2018. Registration number: NTR7129 .

Objectives: To assess the discriminative power of a 5-min quantitative double-echo steady-state (qDESS) sequence for simultaneous T 2 measurements of cartilage and meniscus, and structural knee osteoarthritis (OA) assessment, in a clinical OA population, using radiographic knee OA as reference standard., Methods: Fifty-three subjects were included and divided over three groups based on radiographic and clinical knee OA: 20 subjects with no OA (Kellgren-Lawrence grade (KLG) 0), 18 with mild OA (KLG2), and 15 with moderate OA (KLG3). All patients underwent a 5-min qDESS scan. We measured T 2 relaxation times in four cartilage and four meniscus regions of interest (ROIs) and performed structural OA evaluation with the MRI Osteoarthritis Knee Score (MOAKS) using qDESS with multiplanar reformatting. Between-group differences in T 2 values and MOAKS were calculated using ANOVA. Correlations of the reference standard (i.e., radiographic knee OA) with T 2 and MOAKS were assessed with correlation analyses for ordinal variables., Results: In cartilage, mean T 2 values were 36.1 ± SD 4.3, 40.6 ± 5.9, and 47.1 ± 4.3 ms for no, mild, and moderate OA, respectively (p < 0.001). In menisci, mean T 2 values were 15 ± 3.6, 17.5 ± 3.8, and 20.6 ± 4.7 ms for no, mild, and moderate OA, respectively (p < 0.001). Statistically significant correlations were found between radiographic OA and T 2 and between radiographic OA and MOAKS in all ROIs (p < 0.05)., Conclusion: Quantitative T 2 and structural assessment of cartilage and meniscus, using a single 5-min qDESS scan, can distinguish between different grades of radiographic OA, demonstrating the potential of qDESS as an efficient tool for OA imaging., Key Points: • Quantitative T 2 values of cartilage and meniscus as well as structural assessment of the knee with a single 5-min quantitative double-echo steady-state (qDESS) scan can distinguish between different grades of knee osteoarthritis (OA). • Quantitative and structural qDESS-based measurements correlate significantly with the reference standard, radiographic degree of OA, for all cartilage and meniscus regions. • By providing quantitative measurements and diagnostic image quality in one rapid MRI scan, qDESS has great potential for application in large-scale clinical trials in knee OA.

Background: One of the main determinants of treatment satisfaction after total knee arthroplasty (TKA) is the fulfillment of preoperative expectations. For optimal expectation management, it is useful to accurately predict the treatment result. Multiple patient factors registered in the Dutch Arthroplasty Register (LROI) can potentially be utilized to estimate the most likely treatment result. The aim of the present study is to create and validate models that predict residual symptoms for patients undergoing primary TKA for knee osteoarthritis., Methods: Data were extracted from the LROI of all TKA patients who had preoperative and postoperative patient-reported outcome measures registered. Multivariable logistic regression analyses were performed to construct predictive algorithms for satisfaction, treatment success, and residual symptoms concerning pain at rest and during activity, sit-to-stand movement, stair negotiation, walking, performance of activities of daily living, kneeling, and squatting. We assessed predictive performance by examining measures of calibration and discrimination., Results: Data of 7071 patients could be included for data analysis. Residual complaints on kneeling (female 72%/male 59%) and squatting (female 71%/male 56%) were reported most frequently, and least residual complaints were scored for walking (female 16%/male 12%) and pain at rest (female 18%/male 14%). The predictive algorithms were presented as clinical calculators that present the probability of residual symptoms for an individual patient. The models for residual symptoms concerning sit-to-stand movement, stair negotiation, walking, activities of daily living, and treatment success showed acceptable discriminative values (area under the curve 0.68-0.74). The algorithms for residual complaints regarding kneeling, squatting, pain, and satisfaction showed less favorable results (area under the curve 0.58-0.64). The calibration curves showed adequate calibration for most of the models., Conclusion: A considerable proportion of patients have residual complaints after TKA. The present study showed that demographic and patient-reported outcome measure data collected in the LROI can be used to predict the probability of residual symptoms after TKA. The models developed in the present study predict the chance of residual symptoms for an individual patient on 10 specific items concerning treatment success, functional outcome, and pain relief. This prediction can be useful for individualized expectation management in patients planned for TKA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate in vivo T 2 mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T 2 relaxation time and degree of histological degeneration as reference standard., Methods: In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent pre-operative magnetic resonance imaging using a 3-T MR scanner which included a T 2 mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T 2 relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T 2 mapping and histology was assessed using a generalized least squares model fit by maximum likelihood., Results: The mean T 2 relaxation time was 22.4 ± 2.7 ms (range 18.5-27). The median histological score was 10, IQR 7-11 (range 4-13). A strong correlation between T 2 relaxation time and histological score was found (r s  = 0.84, CI 95% 0.64-0.93)., Conclusion: In vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T 2 mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA., Key Points: • Prospective histology-based study showed that in vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration. • Meniscal T 2 mapping allows detection and quantifying of compositional changes, without need for contrast or special MRI hardware. • Meniscal T 2 mapping provides a biomarker for early OA, potentially allowing early treatment strategies and prevention of OA progression.

Purpose: The Osteoarthritis Research Society International has identified a core set of performance-based tests of physical function for use in people with knee osteoarthritis (OA). The core set consists of the 30-second chair stand test (30-s CST), 4 × 10 m fast-paced walk test (40 m FPWT) and a stair climb test. The aim of this study was to evaluate the reliability, validity and responsiveness of these performance-based measures to assess the ability to measure physical function in knee OA patients., Methods: A prospective cohort study of 85 knee OA patients indicated for total knee arthroplasty (TKA) was performed. Construct validity and responsiveness were assessed by testing of predefined hypotheses. A subgroup (n = 30) underwent test-retest measurements for reliability analysis. The Oxford Knee Score, Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form, pain during activity score and knee extensor strength were used as comparator instruments. Measurements were obtained at baseline and 12 months after TKA., Results: Appropriate test-retest reliability was found for all three tests. Intraclass correlation coefficient (ICC) for the 30-s CST was 0.90 (95% CI 0.68; 0.96), 40 m FPWT 0.93 (0.85; 0.96) and for the 10-step stair climb test (10-step SCT) 0.94 (0.89; 0.97). Adequate construct validity could not be confirmed for the three tests. For the 30-s CST, 42% of the predefined hypotheses were confirmed; for the 40 m FPWT, 27% and for the 10-step SCT 36% were confirmed. The 40 m FPWT was found to be responsive with 75% of predefined hypothesis confirmed, whereas the responsiveness for the other tests could not be confirmed. For the 30 s CST and 10-step SCT, only 50% of hypotheses were confirmed., Conclusions: The three performance-based tests had good reliability, but poor construct validity and responsiveness in the assessment of function for the domains sit-to-stand movement, walking short distances and stair negotiation. The findings of the present study do not justify their use for clinical practice., Level of Evidence: Level 1. Diagnostic study.

Background: High molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated., Methods: In this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient's global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed., Results: In total, 156 subjects were included (intervention group 77, control group 79). Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2% (p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest (δ 0.8, 95%CI 0.2; 1.4, p = 0.010), knee related function (δ - 6.8, 95%CI -11.9; - 1.7, p = 0.010) and PGA (δ - 0.7, 95%CI -0.9; - 0.4, p < 0.0001)., Conclusions: Intra-articular HMW-HA added to usual care is effective for knee OA in patients in the working age., Trial Registration: www.trialregister.nl , NTR1651, registered 2009-3-3.

Background: One out of five patients is unsatisfied to some extent after total knee arthroplasty (TKA). Unmet expectations are the main driver of post-operative dissatisfaction. Improved pre-operative education on realistic expectations for long-term outcome after TKA potentially leads to higher post-operative satisfaction. The effect of expectation modification on post-operative satisfaction in TKA patients has not yet been studied. The primary objective of the presented study is to examine whether an educational module on long-term recovery after TKA will improve patient satisfaction compared to usual pre-operative education., Methods: The EKSPECT study is a randomized controlled trial. Patients with symptomatic and radiographic knee osteoarthritis who are indicated for a primary TKA will be randomized to the usual pre-operative education (control group) or usual education plus an additional module on realistic expectations for long-term recovery (intervention group). Patients will be naïve to study objective and difference between study groups. Outcome expectations will be measured blinded for group allocation using the HSS Knee Replacement Expectations Survey at baseline (before the intervention), pre-operatively (after the intervention) and fulfillment of expectations at 12-month follow-up. Baseline physical function, quality of life and psychological factors are measured using self-reported questionnaires. The primary outcome measure is satisfaction with treatment result at the 12-month follow-up., Discussion: The EKSPECT study should provide evidence on the effectiveness of an education module on long-term recovery after TKA to improve treatment satisfaction. If beneficial, the education module is a simple intervention with a low burden for patients, which can easily be implemented in clinical practice., Trial Registration: Dutch Trial Registry registration number: NTR5779 . Registered on 17 March 2016.

Objective: Knee osteoarthritis (OA) is associated with high medical costs and especially with high productivity costs, in particular in patients in their working years. High molecular weight (HMW) hyaluronic acid (HA) is an alternative treatment for nonsteroidal antiinflammatory drugs, which are known for their serious side-effects. The cost-utility of intraarticular HMW-HA treatment in these patients is unknown, however, and was assessed in this study., Methods: Secondary care patients ages 18-65 years with knee OA were randomized to usual care plus HMW-HA (intervention group) or to usual care only (control group). A cost-utility analysis over 52 weeks from the societal and health care perspective was performed. Uncertainty for costs, effects, and cost-utility ratio was analyzed by nonparametric bootstrapping. Baseline imbalance adjustment was done by inverse probability of treatment weighting., Results: In total, 156 subjects were included (intervention group n = 77, control group n = 79). The total of productivity and medical costs was €475 higher in the intervention group at €7,754 (95% confidence interval [95% CI] 5,426, 10,436) versus €7,270 (95% CI 5,453, 9,262). The amount of quality-adjusted life years (QALYs) gained during followup was also higher in the intervention group (0.779 versus 0.727). This variation resulted in an incremental cost-effectiveness ratio of €9,100/QALY from a societal perspective and €8,700/QALY from a health care perspective. When the maximum willingness to pay for conditions similar to knee OA is considered, the probability on cost-effectiveness is 64% and 86%, respectively., Conclusion: Intraarticular HMW-HA added to usual care for knee OA is probably cost-effective in the treatment of knee OA., (© 2017, American College of Rheumatology.)

Objective: No randomized controlled trial (RCT) has compared the high tibial osteotomy (HTO) with non-surgical treatment in patients with medial knee osteoarthritis (OA) and varus malalignment. The aim was to compare the effectiveness of an unloader brace treatment or a usual care program to the HTO regarding pain severity and knee function., Design: Surgical treatment (HTO) to two non-surgical options was compared by combining the data of two RCTs. One RCT (n = 117) compared an unloader brace to usual care treatment; the other RCT (n = 92) compared closing to opening wedge HTO. One-to-many propensity score matching was used to equalize patient characteristics. We compared clinical outcome at 1 year follow-up (VAS pain (0-10) and knee function (HSS, 0-100)) with mixed model analysis., Results: Propensity score matching resulted in a comparison of 30 brace patient with 83 HTO patients, and of 28 usual care patients with 71 HTO patients. Pain at 1 year after HTO (VAS 3.8) was lower than after valgus bracing (VAS 5.0) with a mean difference of -1.1 (95% CI -2.2; -0.1). Function showed a nonsignificant mean difference of 2.1 [95% CI -3.1; 7.3]. Comparing HTO to usual care a difference was seen in pain (-1.7 [95% CI -2.8; -0.6]) and function (6.6 [95% CI 0.2; 13.1]), in favor of the HTO., Conclusions: Our data suggest that HTO was more effective in pain reduction compared to both non-surgical treatments. Function improved only when HTO was compared to usual care treatment. These small differences question the benefits of surgical treatment over the brace treatment., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T)., Design: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC)., Results: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC., Conclusion: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: Varus medial knee osteoarthritis (OA) can be treated with a closing-wedge (CW) or opening-wedge (OW) high tibial osteotomy (HTO). Little is known about the adverse event (AE) rate of these techniques. The purpose of this study was to examine the AE rate and survival rate of a consecutive series of 412 patients undergoing CW- or OW-HTO., Methods: Medical records were retrospectively screened, and all patients who underwent HTO from 1993 to 2012 at the Erasmus University Medical Centre were assessed with a self-administered questionnaire. Patients filled in the intermittent and constant osteoarthritis pain score, knee injury and osteoarthritis outcome score, and a general questionnaire focusing on AE., Results: Medical records of 412 patients (354 CW- and 112 OW-HTOs) were screened. Of the 358 eligible patients, 291 (81 %) returned their questionnaire. A total of 80 AE (17 %) were found in 466 osteotomies. In the CW-group, 47 (13 %) serious adverse events (SAE) and 2 (0.6 %) AE were found. In the OW-group, 17 (15 %) SAE and 14 (13 %) AE were found. The most common AE was in 14 (4 %) patients of the CW-group sensory palsy of the common peroneal nerve. The most common AE in the OW-group was persistent pain at the iliac crest [11 (9.8 %) patients]. Hardware was removed in 48 % of the CW-osteotomies and 71 % of the OW-osteotomies (p < 0.05). The probability of survival was 75 % after 10 years in the CW-group versus 90 % in the OW-group (p < 0.05). In both groups, an equal number of patients were "in need for prosthesis" according to OARSI criteria., Conclusion: OW-HTO was associated with more AE than CW-HTO. OW-HTO resulted in better survival than CW-HTO. However, in both groups an equal number of patients were in need for prosthesis., Level of Evidence: Retrospective comparative study, Level III.

Background: Anterior cruciate ligament (ACL) rupture is a well-known risk factor for development of knee osteoarthritis. Early identification of those patients at risk and early identification of the process of ACL rupture leading to osteoarthritis may aid in preventing the onset or progression of osteoarthritis., Purpose: To identify early degenerative changes as assessed on magnetic resonance imaging (MRI) after 2-year follow-up in patients with a recent ACL rupture and to evaluate which determinants are related to these changes., Study Design: Cohort study; Level of evidence, 2., Methods: Included in this study were 154 adults aged between 18 and 45 years with acute ACL rupture diagnosed by physical examination and MRI, without previous knee trauma or surgery, and without osteoarthritic changes on radiographs. A total of 143 patients completed the 2-year follow-up, and the results in this study apply to these 143 patients. All patients were treated according to the Dutch guideline on ACL injury. Of the 143 patients, 50 patients were treated nonoperatively during the 2-year follow-up period. Main outcome was early degenerative changes assessed on MRI defined as progression of cartilage defects and osteophytes in tibiofemoral and patellofemoral compartments. Patient characteristics, activity level, functional instability, treatment type, and trauma-related variables were evaluated as determinants., Results: The median time between MRI at baseline and MRI at 2-year follow-up was 25.9 months (interquartile range, 24.7-26.9 months). Progression of cartilage defects in the medial and lateral tibiofemoral compartments was present in 12% and 27% of patients, and progression of osteophytes in tibiofemoral and patellofemoral compartments was present in 10% and 8% of patients, respectively. The following determinants were positively significantly associated with early degenerative changes: male sex (odds ratio [OR], 4.43; 95% CI, 1.43-13.66; P = .010), cartilage defect in the medial tibiofemoral compartment at baseline (OR, 3.66; 95% CI, 1.04-12.95; P = .044), presence of bone marrow lesions in the medial tibiofemoral compartment 1 year after trauma (OR, 5.19; 95% CI, 1.56-17.25; P = .007), joint effusion 1 year after trauma (OR, 4.19; 95% CI, 1.05-16.72; P = .042), and presence of meniscal tears (OR, 6.37; 95% CI, 1.94-20.88; P = .002). When the patients were categorized into 3 treatment groups (nonoperative, reconstruction <6 months after ACL rupture, and reconstruction ≥6 months after ACL rupture), there was no significant relationship between the treatment options and the development of early degenerative changes., Conclusion: Two years after ACL rupture, early degenerative changes were assessed on MRI. Concomitant medial cartilage defect and meniscal injury, male sex, persistent bone marrow lesions in the medial tibiofemoral compartment, and joint effusion are risk factors for degenerative changes., (© 2016 The Author(s).)

Purpose: To determine if T1ρ mapping can be used as an alternative to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the quantification of cartilage biochemical composition in vivo in human knees with osteoarthritis., Materials and Methods: This study was approved by the institutional review board. Written informed consent was obtained from all participants. Twelve patients with knee osteoarthritis underwent dGEMRIC and T1ρ mapping at 3.0 T before undergoing total knee replacement. Outcomes of dGEMRIC and T1ρ mapping were calculated in six cartilage regions of interest. Femoral and tibial cartilages were harvested during total knee replacement. Cartilage sulphated glycosaminoglycan (sGAG) and collagen content were assessed with dimethylmethylene blue and hydroxyproline assays, respectively. A four-dimensional multivariate mixed-effects model was used to simultaneously assess the correlation between outcomes of dGEMRIC and T1ρ mapping and the sGAG and collagen content of the articular cartilage., Results: T1 relaxation times at dGEMRIC showed strong correlation with cartilage sGAG content (r = 0.73; 95% credibility interval [CI] = 0.60, 0.83) and weak correlation with cartilage collagen content (r = 0.40; 95% CI: 0.18, 0.58). T1ρ relaxation times did not correlate with cartilage sGAG content (r = 0.04; 95% CI: -0.21, 0.28) or collagen content (r = -0.05; 95% CI = -0.31, 0.20)., Conclusion: dGEMRIC can help accurately measure cartilage sGAG content in vivo in patients with knee osteoarthritis, whereas T1ρ mapping does not appear suitable for this purpose. Although the technique is not completely sGAG specific and requires a contrast agent, dGEMRIC is a validated and robust method for quantifying cartilage sGAG content in human osteoarthritis subjects in clinical research., ((©) RSNA, 2015.)

Objective: To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA)., Design: Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index ≥ 27 kg/m(2) without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0 mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses., Results: 254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome., Conclusions: In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associated with an increased risk for incident knee OA. This interesting but counterintuitive outcome makes further validation of this biomarker warranted., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: With accumulating knowledge on osteoarthritis development, the next step is to focus on possibilities for primary prevention., Methods: In a 2 × 2 factorial design, the effects of a diet-and-exercise program and of oral glucosamine sulfate (double blind and placebo-controlled) on the incidence of knee osteoarthritis were evaluated in a high-risk group of 407 middle-aged women with a body mass index ≥ 27 kg/m(2) without clinical signs of knee osteoarthritis at baseline (ISRCTN 42823086). Primary outcome was the incidence of knee osteoarthritis, defined as Kellgren & Lawrence grade ≥ 2, joint space narrowing of ≥ 1.0 mm, or clinical knee osteoarthritis (clinical and radiographic American College of Rheumatology criteria) after 2.5 years., Results: After 2.5 years, only 10% of all subjects were lost to follow-up, and 17% of all knees showed incident knee osteoarthritis. Accounting for the significant interaction between the interventions, no significant main effect of either intervention was found. Independently, both interventions alone showed indications of reduced knee osteoarthritis incidence (odds ratio [OR] 0.69; 95% CI, 0.39-1.21 for the diet-and-exercise program and OR 0.60; 95% CI, 0.31-1.12 for the glucosamine intervention). These effects were neutralized in subjects receiving both interventions (OR 0.97; 95% CI, 0.55-1.71)., Conclusions: No significant main effects of the diet-and-exercise program and of glucosamine sulfate were found on incident knee osteoarthritis. Nevertheless, this trial provides valuable insights for future trial design for preventive osteoarthritis studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Anterior cruciate ligament (ACL) injury is an important risk factor for development of knee osteoarthritis (OA). To identify those ACL injured patients at increased risk for knee OA, it is necessary to understand risk factors for OA., Aim: To summarise the evidence for determinants of (1) tibiofemoral OA and (2) patellofemoral OA in ACL injured patients., Methods: MEDLINE, EMBASE, Web of Science and CINAHL databases were searched up to 20 December 2013. Additionally, reference lists of eligible studies were manually and independently screened by two reviewers. 2348 studies were assessed for the following main inclusion criteria: ≥20 patients; ACL injured patients treated operatively or non-operatively; reporting OA as outcome; description of relationship between OA outcome and determinants; and a follow-up period ≥2 years. Two reviewers extracted the data, assessed the risk of bias and performed a best-evidence synthesis., Results: Sixty-four publications were included and assessed for quality. Two studies were classified as low risk of bias. Medial meniscal injury/meniscectomy showed moderate evidence for influencing OA development (tibiofemoral OA and compartment unspecified). Lateral meniscal injury/meniscectomy showed moderate evidence for no relationship (compartment unspecified), as did time between injury and reconstruction (tibiofemoral and patellofemoral OA)., Conclusions: Medial meniscal injury/meniscectomy after ACL rupture increased the risk of OA development. In contrast, it seems that lateral meniscal injury/meniscectomy has no relationship with OA development. Our results suggest that time between injury and reconstruction does not influence patellofemoral and tibiofemoral OA development. Many determinants showed conflicting and limited evidence and no determinant showed strong evidence., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The results of conservative treatment of knee osteoarthritis (OA) are generally evaluated in epidemiological studies with clinical outcome measures as primary outcomes. Biomechanical evaluation of orthoses shows that there are potentially beneficial biomechanical changes to joint loading; however, evaluation in relation to clinical outcome measures in longitudinal studies is needed., Questions/purposes: We asked (1) is there an immediate effect on gait in patients using a laterally wedged insole or valgus knee brace; (2) is there a late (6 weeks) effect; and (3) is there a difference between subgroups within each group with respect to patient compliance, body mass index, and OA status?, Methods: This was a secondary analysis of data from a previous randomized controlled trial of patients with early medial knee OA. A total of 91 patients were enrolled in that trial, and 73 (80%) completed it after 6 months. Of the enrolled patients, 80 (88%) met prespecified inclusion criteria for analysis in the present study. The patients were randomized to an insole or brace. Gait was analyzed with and without wearing the orthosis (insole or brace) at baseline and after 6 weeks. Measurements were taken of the knee adduction moment, ground reaction force, moment arm, walking speed, and toe-out angle. Data were analyzed with regression analyses based on an intention-to-treat principle., Results: A mean reduction of 4% (±10) (95% confidence interval [CI], -0.147 to -0.03, p=0.003) of the peak knee adduction moment and 4% (±13) (95% CI, -0.009 to -0.001, p=0.01) of the moment arm at baseline was observed in the insole group when walking with an insole was compared with walking without an insole. A mean reduction of 1% (±10) (95% CI, -0.002 to -0.001, p=0.001) of the peak knee adduction moment and no reduction of the moment arm were measured after 6 weeks. No reduction of knee adduction moment, moment arm, or ground reaction force was seen in the brace group at baseline and after 6 weeks. Subgroup analysis showed no differences in biomechanical effect for obesity, stage of OA, and whether patients showed a clinical response to the treatment., Conclusions: Laterally wedged insoles unload the medial compartment only at baseline in patients with varus alignment and by an amount that might not be clinically important. No biomechanical alteration was seen after 6 weeks of wearing the insole. Valgus brace therapy did not result in any biomechanical alteration. Taken together, this study does not show a clinically relevant biomechanical effect of insole and brace therapy in patients with varus medial knee OA., Level of Evidence: Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Objective: Recently, the MRI Osteoarthritis Knee Score (MOAKS), a new semi-quantitative magnetic resonance imaging (MRI) scoring tool, was introduced by a panel of experienced researchers in osteoarthritis (OA). The MOAKS is primarily applicable to quantify OA status, since the interpretation of change in the MOAKS features was not described. In order to enable longitudinal evaluation, we propose definitions for progression and improvement of the main MOAKS features., Method: Clear definitions for progression and improvement of the main MOAKS features are given in this brief report. 687 baseline and 30 months follow-up MRIs of the knees of 348 overweight and obese middle-aged women, free of OA at baseline, were scored using the MOAKS. Baseline prevalence and the change of MOAKS features after 30 months follow-up, based on our definitions for progression and improvement, are presented., Results: The proposed definitions showed 3% to 23% progression and 0% to 11% improvement in the MOAKS features during the 30 months follow-up. Overall, progression rates were higher in the medial than in the lateral tibiofemoral (TF) joint. Progression of bone marrow lesions (BMLs) and cartilage defects was highest in the patellofemoral (PF) joint. Inter-rater reliability of the MOAKS scores was moderate to nearly perfect (PABAK 0.77-0.88), with high percentage of agreement overall (89-94%)., Conclusion: This brief report presents definitions for progression and improvement of the main MOAKS features for the longitudinal evaluation of knee OA features on MRI. We advocate uniform usage of the proposed definitions across studies, but welcome suggestions for optimization., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Varus deformity increases the risk of progression of medial compartment knee osteoarthritis. The aim of this study was to investigate the clinical and radiographic mid-term results of closing-wedge and opening-wedge high tibial osteotomy when used to treat this condition., Methods: From January 2001 to April 2004, ninety-two patients were randomized to receive either a closing-wedge or an opening-wedge high tibial osteotomy. The clinical outcome and radiographic results were examined preoperatively; at one year; and, for the present study, at six years postoperatively. The outcomes that we reviewed included maintenance of the achieved correction, progression of osteoarthritis (based on the Kellgren and Lawrence classification), severity of pain (as assessed on a visual analog scale [VAS]), knee function (as measured with the Hospital for Special Surgery [HSS] score and Knee injury and Osteoarthritis Outcome Score [KOOS]), walking distance, complications, and survival with conversion to a total knee arthroplasty as the end point. The results were analyzed on the basis of the intention-to-treat principle., Results: Six years postoperatively, the mean hip-knee-ankle (HKA) angle (and standard deviation) was 3.2° ± 4.1° of valgus after a closing-wedge high tibial osteotomy and 1.3° ± 5.0° of valgus after an opening-wedge high tibial osteotomy (p = 0.343). In both groups, the six-year postoperative HKA angles did not differ from the respective one-year postoperative angles. No difference in the severity of pain or in knee function was found between the two groups. Four complications (9%) occurred in the closing-wedge group and seventeen (38%), in the opening-wedge group. Ten (22%) of the patients in the closing-wedge group and three (8%) in the opening-wedge group needed conversion to a total knee arthroplasty within the six-year period (p = 0.05). The difference in the percentage of cases with conversion to total knee arthroplasty was 14% (95% confidence interval [CI] = 21.7 to 0.2)., Conclusions: In the group of patients without conversion to a total knee arthroplasty, there was no difference between the high tibial closing-wedge and opening-wedge osteotomies in terms of clinical outcomes or radiographic alignment at six years postoperatively. Opening-wedge osteotomy was associated with more complications, but closing-wedge osteotomy was associated with more early conversions to total knee arthroplasty., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: The present study aims to investigate the associations between malalignment and incident knee OA after 2.5 years in a high-risk group of 333 middle-aged overweight women (BMI ≥ 27 kg/m(2)) free of clinical and radiological knee OA at baseline., Methods: The primary outcome measure was the incidence of knee OA, defined as the incidence of radiographic knee OA (Kellgren and Lawrence grade ≥2), clinical knee OA (ACR criteria) or medial or lateral joint space narrowing (≥1.0 mm). Using generalized estimating equations, associations between valgus and varus alignment (compared with neutrally aligned knees) and the primary outcome measure and all its items separately were studied., Results: Neither varus- nor valgus-aligned knees had a significantly increased risk for incident knee OA according to the primary outcome measure. A significantly increased risk for the development of radiographic knee OA was found for varus-aligned knees [odds ratio (OR) 3.3, 95% CI 1.5, 7.3]. Valgus-aligned knees showed a borderline increased OR (2.8, 95% CI 1.0, 8.0) for the development of radiographic knee OA. No statistically significant effects were found for varus and valgus alignment on the incidence of clinical knee OA or medial or lateral joint space narrowing., Conclusion: Since this study was performed in a true target population, current data suggest that malalignment might be a target for the prevention of radiographic knee OA in overweight and obese women., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To assess (1) whether normal and degenerated menisci exhibit different T1GD on delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM), (2) the reproducibility of dGEMRIM and (3) the correlation between meniscus and cartilage T1GD in knee osteoarthritis (OA) patients., Methods: In 17 OA patients who underwent dGEMRIM twice within 7 days, meniscus and cartilage T1GD was calculated. Meniscus pathology was evaluated on conventional MRI. T1GD in normal and degenerated menisci were compared using a Student's t-test. Reproducibility was assessed using ICCs. Pearson's correlation was calculated between meniscus and cartilage T1GD., Results: A trend towards lower T1GD in degenerated menisci (mean: 402 ms; 95% CI: 359-444 ms) compared to normal menisci (mean: 448 ms; 95% CI: 423-473 ms) was observed (p = 0.05). Meniscus T1GD ICCs were 0.85-0.90. The correlation between meniscus and cartilage T1GD was moderate in the lateral (r = 0.52-0.75) and strong in the medial compartment (r = 0.78-0.94)., Conclusions: Our results show that degenerated menisci have a clear trend towards lower T1GD compared to normal menisci. Since these results are highly reproducible, meniscus degeneration may be assessed within one delayed gadolinium-enhanced MRI simultaneously with cartilage. The strong correlation between meniscus and cartilage T1GD suggests concomitant degeneration in both tissues in OA, but also suggests that dGEMRIC may not be regarded entirely as sulphated glycosaminoglycan specific., Key Points: dGEMRIM T1 GD can possibly be used to assess meniscal degeneration; dGEMRIM yields highly reproducible meniscal T1 GD in early stage osteoarthritic patients; Concomitant degeneration of cartilage and meniscus tissue occurs in early stage osteoarthritis; dGEMRIC cannot be regarded as entirely sulphated glycosaminoglycan specific.

Background: A subset of patients with total hip arthroplasty (THA) or total knee arthroplasty (TKA) has suboptimal postoperative results in terms of Patient Reported Outcomes (PROs), and psychological factors could contribute to these suboptimal results., Objectives: To examine the prevalence of anxiety and depressive symptoms in patients undergoing primary THA or TKA preoperatively and postoperatively, and the relationship between preoperative anxiety and depressive symptoms on PROs of THA and TKA., Design: In this prospective study patients were measured preoperatively, and 3 and 12 months postoperatively. Patients filled in the Hospital Anxiety and Depression Scale, Knee injury and Osteoarthritis Outcome Score (KOOS) or Hip disability and Osteoarthritis Outcome Score (HOOS) and a satisfaction questionnaire., Results: Data were obtained from 149 hip and 133 knee patients. The prevalence of anxiety symptoms decreased significantly from 27.9% to 10.8% 12 months postoperatively in hip patients, and from 20.3% to 14.8% in knee patients. Depressive symptoms decreased significantly from 33.6% to 12.1% 12 months postoperatively in hip patients, and from 22.7% to 11.7% in knee patients. In hip and knee patients, preoperative depressive symptoms predicted smaller changes in different HOOS or KOOS subscales and patients were less satisfied 12 months postoperatively., Conclusions: Preoperatively, the prevalence of anxiety and depressive symptoms was high. At 3 and 12 months postoperatively, the prevalence of anxiety and depressive symptoms was decreased in both hip and knee patients. However, patients with preoperative anxiety and depressive symptoms had worse PROs 3 and 12 months after THA and TKA and were less satisfied than patients without anxiety or depressive symptoms., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Introduction: Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA., Methods: In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses., Results: All KOOS subscales ('pain', 'symptoms', 'daily activities', 'sports' and 'quality of life') and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee., Conclusions: Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.

Our previous study showed that 6 months after total hip arthroplasty (THA) or total knee arthroplasty (TKA), patients reported having less difficulty with daily activities, showed better functional capacity, and performed activities in their natural environment faster compared to preoperatively. However, their actual daily activity level was not significantly improved. Six months is a rather short follow-up period and the discrepancy in recovery among different aspects of functioning might be explained by this limited duration of follow-up. The objective of the present study was to examine the recovery of different aspects of physical functioning at a follow-up nearly 4 years after THA/TKA. Special attention was given to the actual daily activity level, and whether it had increased 4 years after THA/TKA compared to 6 months postoperatively. Seventy-seven (35 hip, 42 knee) patients who were measured preoperatively and postoperatively (6 months after surgery) in a previous study were invited to participate; 44 patients (23 hip, 21 knee) agreed to participate. The 4-year follow-up data were compared with the preoperative and 6-month postoperative data. The daily activity level after 4 years was found to be actually lower than at 6 months post-surgery (128 min vs. 138 min activity per 24h; p-value 0.48). However, the patients continued to improve in other aspects of physical functioning. In conclusion, 4-year post-surgery patients continued to improve on perceived physical functioning, capacity, and performance of activities in daily life. However, even in this relatively healthy study population, patients did not adopt a more active lifestyle 4 years after surgery., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA., Design: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed., Results: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis., Conclusion: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess the reproducibility of 3D delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 3 T in early stage knee osteoarthritis (OA) patients., Methods: In 20 patients, 3D dGEMRIC at 3 T was acquired twice within 7 days. To correct for patient motion during acquisition, all images were rigidly registered in 3D. Eight anatomical cartilage ROIs were analysed on both images of each patient. Capability of dGEMRIC to yield T1 maps that reproducibly distinguish spatial differences in cartilage quality was assessed in two ROIs within a single slice in each patient. Reproducibility was assessed using ICCs and Bland-Altman plots., Results: ICCs ranged from 0.87 to 0.95, indicating good reproducibility. T1 maps revealed reproducible spatial differences in cartilage quality (ICC 0.79). Based on the Bland-Altman plots, we defined a threshold of 95 ms to determine if a change in dGEMRIC outcome in longitudinal research was statistically significant., Conclusions: 3D knee dGEMRIC at 3 T combined with 3D image registration is a highly reproducible measure of cartilage quality in early stage OA. Therefore, dGEMRIC may be a valuable tool in the non-invasive evaluation of cartilage quality changes in longitudinal research in patients with early stage OA and focal cartilage defects.

Objective: To assess a wide spectrum of biochemical markers (biomarkers) in a large cohort of individuals with (very) early symptomatic knee and/or hip osteoarthritis (OA). Secondly, to investigate associations between biomarkers and between biomarkers and demographics to demonstrate validity of the obtained dataset and further investigate the involvement and/or role of these biomarkers in OA., Design: Fourteen biomarkers (uCTX-II, uCTX-I, uNTX-I, sCOMP, sPIIANP, sCS846, sC1,2C, sOC, sPINP, sHA, sPIIINP, pLeptin, pAdiponectin, pResistin) were assessed by ELISA or RIA in CHECK (Cohort Hip and Cohort Knee), a 10-year prospective cohort of 1,002 individuals with early symptomatic knee and/or hip OA., Results: Quality controls revealed that gathered data were technically reliable. The majority of biomarkers showed relevant associations with demographic variables, which were expectedly different between genders and/or menopausal status for some. Principal component analysis enabled identification of five clusters, consecutively designated as 'bone-CTX-II', 'inflammation', 'synovium', 'C1,2C-adipokines', and 'cartilage synthesis' cluster. Notably, uCTX-II clustered with biomarkers of bone metabolism, while sCOMP clustered with biomarkers of synovial activity., Conclusions: The identified clusters extended knowledge on individual biomarkers from mostly smaller studies as did the observed associations between biomarker levels and demographics, from which validity of our data was deduced. uCTX-II may not only reflect articular cartilage but also bone metabolism and sCOMP may reflect synovial rather than cartilage metabolism. Major involvement of adipokines in joint metabolism was not identified., (Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Although the knee joint is one of the joints most affected by osteoarthritis (OA), research on the economic implications of joint disease has generally focused only on OA. The goal of this study was to identify and quantify knee-related productivity and medical costs in knee OA patients with paid employment. Furthermore, we evaluated associations between productivity loss and relevant patient, health, and work characteristics., Methods: Consecutive knee OA patients with mild to moderate knee OA who were 18-65 years of age, had conservative treatment for ≥6 months, and had paid employment were included. Productivity loss and health care consumption were measured by questionnaires. The associations between productivity loss and patient, health, and work characteristics were explored with regression analyses., Results: In total, 117 knee OA patients with a mean age of 53.2 years and a mean body mass index of 28.8 kg/m(2) were included. Total knee-related productivity costs and medical costs were €871 (median €411, interquartile range [IQR] €107-1,200) per patient per month, with total productivity costs of €722 (median €217, IQR €0-1,041) and total medical costs of €149 (median €137, IQR €72-198). More pain during activity and performing physically intensive work were significantly associated with productivity loss., Conclusion: The total knee-related productivity costs and medical costs of conservatively treated symptomatic knee OA patients with paid employment in The Netherlands are €871 per patient per month, with productivity costs accounting for 83% and medical costs for 17%. Productivity loss is associated with having more pain during activity and performing physically intensive work. Developing adequate treatment strategies for knee OA may be cost beneficial., (Copyright © 2012 by the American College of Rheumatology.)

Background: There is controversial evidence regarding whether foot orthoses or knee braces improve pain and function or correct malalignment in selected patients with osteoarthritis (OA) of the medial knee compartment. However, insoles are safe and less costly than knee bracing if they relieve pain or improve function., Questions/purposes: We therefore asked whether laterally wedged insoles or valgus braces would reduce pain, enhance functional scores, and correct varus malalignment comparable to knee braces., Patients and Methods: We prospectively enrolled 91 patients with symptomatic medial compartmental knee OA and randomized to treatment with either a 10-mm laterally wedged insole (index group, n = 45) or a valgus brace (control group, n = 46). All patients were assessed at 6 months. The primary outcome measure was pain severity as measured on a visual analog scale. Secondary outcome measures were knee function score using WOMAC and correction of varus alignment on AP whole-leg radiographs taken with the patient in the standing position. Additionally, we compared the percentage of responders according to the OMERACT-OARSI criteria for both groups., Results: We observed no differences in pain or WOMAC scores between the two groups. Neither device achieved correction of knee varus malalignment in the frontal plane. According to the OMERACT-OARSI criteria, 17% of our patients responded to the allocated intervention. Patients in the insole group complied better with their intervention. Although subgroup analysis results should be translated into practice cautiously, we observed a slightly higher percentage of responders for the insole compared with bracing for patients with mild medial OA., Conclusions: Our data suggest a laterally wedged insole may be an alternative to valgus bracing for noninvasively treating symptoms of medial knee OA., Level of Evidence: Level I, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.

Surgical therapeutic procedures such as knee osteotomy and knee replacement depend on proper knee alignment assessment. The aim of this study was to evaluate if femorotibial (FT) measurement on short knee films may be used in clinical settings. The study population comprised 68 patients with symptomatic medial compartmental knee osteoarthritis. We measured the FT angle with the use of mid-diaphyseal lines (FTa), and the knee joint centre (FTb) to determine anatomical knee alignment on a short knee image. Then, the accuracy of alignment was compared to the gold standard Hip-Knee-Ankle (HKA) angle on a full-limb view. FTa angle assessment correlated well (r=0.65) with the HKA angle. However, this method showed poor inter-observer agreement (ICC=0.37). 3% of patients were incorrectly classified as having valgus alignment. Good intra- and inter-observer agreements were observed for FTb angle measurement (ICC=0.89 and 0.79; respectively). But correlation between HKA and FTb angles was low (r=0.34). 15% of patients were incorrectly classified as having valgus alignment. Short knee images cannot substitute whole leg views when accurate assessment of knee alignment is essential.

Background and Purpose: The aim with high tibial valgus osteotomy (HTO) is to correct the mechanical axis in medial compartmental osteoarthritis of the knee. Loss of operative correction may threaten the long-term outcome. In both a lateral closing-wedge procedure and a medial opening-wedge procedure, the opposite cortex of the tibia is usually not osteotomized, leaving 1 cm of bone intact as fulcrum. A fracture of this cortex may, however, lead to loss of correction; this was examined in the present study., Patients and Methods: We used a prospective cohort of 92 consecutive patients previously reported by Brouwer et al. (2006). The goal in that randomized controlled trial, was to achieve a correction of 4 degrees in excess of physiological valgus. In retrospect, we evaluated the 1-year radiographic effect of opposite cortical fracture. Opposite cortical fracture was identified on the postero-anterior radiographs in supine position on the first day after surgery., Results: 44 patients with a closing-wedge HTO (staples and cast fixation) and 43 patients with an opening-wedge HTO (non-angular-stable plate fixation) were used for analysis. 36 patients (four-fifths) in the closing-wedge group and 15 patients (one-third) in the opening-wedge group had an opposite cortical fracture (p < 0.001). At 1 year, the closing-wedge group with opposite cortical fracture had a valgus position with a mean HKA angle of 3.2 (SD 3.5) degrees of valgus. However, the opening-wedge group with disruption of the opposite cortex achieved varus malalignment with a mean HKA angle of 0.9 (SD 6.6) degrees of varus., Interpretation: Fracture of the opposite cortex is more common for the lateral closing wedge technique. Medial cortex disruption has no major consequences, however, and does not generally lead to malalignment. Lateral cortex fracture in the medial opening-wedge technique, with the use of a non-angular stable plate, leads more often to varus malalignment.

Background and Purpose: High tibial valgus osteotomy (HTO) is a well-accepted treatment for medial unicompartmental osteoarthritis of the knee with varus alignment in relatively young and active patients. Controversies about the factors affecting survival of HTO still exist. We assessed preoperative risk factors for failure of closing-wedge HTO at long-term follow-up., Patients and Methods: A cohort of 100 patients with a mean age of 49 (24-67) years, who had closing-wedge HTO performed between January 1991 and December 1996, were analyzed retrospectively. A survival analysis was carried out according to the Kaplan-Meier method. Logistic regression analysis was used to assess the association between failure of the osteotomy and known potential preoperative risk factors., Results: The probability of survival for HTO was 75% (SD 4%) at 10 years with knee replacement as the endpoint. Female sex and osteoarthritis of grade > or = 2 were identified as preoperative risk factors for conversion to arthroplasty 10 years after HTO., Interpretation: Our findings suggest that ideal candidates for corrective osteotomy are men with symptomatic medial compartmental osteoarthritis of Ahlback grade 1, who, 10 years after surgery, have an almost tenfold lower probability of failure of HTO than women with more advanced osteoarthritis.

Background: The Knee Injury and Osteoarthritis Outcome Score (KOOS) was constructed in Sweden. This questionnaire has proved to be valid for several orthopedic interventions of the knee. It has been formally translated and validated in several languages, but not yet in Dutch. The purpose of the present study was to evaluate the clinimetric properties of the Dutch version of the KOOS questionnaire in knee patients with various stages of osteoarthritis (OA)., Methods: The Swedish version of the KOOS questionnaire was first translated into Dutch according to a standardized procedure and second tested for clinimetric quality. The study population consisted of patients with different stages of OA (mild, moderate and severe) and of patients after primary TKA, and after a revision of the TKA. All patients filled in the Dutch KOOS questionnaire, as well as the SF-36 and a Visual Analogue Scale for pain. The following analyses were performed to evaluate the clinimetric quality of the KOOS: Cronbach's alpha (internal consistency), principal component analyses (factor analysis), intraclass correlation coefficients (reliability), spearman's correlation coefficient (construct validity), and floor and ceiling effects., Results: For all patients groups Cronbach's alpha was for all subscales above 0.70. The ICCs, assessed for the patient groups with mild and moderate OA and after revision of the TKA patients, were above 0.70 for all subscales. Of the predefined hypotheses 60% or more could be confirmed for the patients with mild and moderate OA and for the TKA patients. For the other patient groups less than 45% could be confirmed. Ceiling effects were present in the mild OA group for the subscales Pain, Symptoms and ADL and for the subscale Sport/Recreation in the severe OA group. Floor effects were found for the subscales Sport/Recreation and Qol in the severe OA and revision TKA groups., Conclusion: Based on these different clinimetric properties within the present study we conclude that the KOOS questionnaire seems to be suitable for patients with mild and moderate OA and for patients with a primary TKA. The Dutch version of the KOOS had a lower construct validity for patients with severe OA on a waiting list for TKA and patients after revision of a TKA. Further validation studies on the Dutch version of the KOOS should also include a knee specific questionnaire for assessing the construct validity.

Objective: Although knee malalignment is assumed to correlate with knee osteoarthritis (OA), it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA. The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA., Methods: A total of 1,501 participants in the Rotterdam study were randomly selected. Knee OA at baseline and at followup (mean followup 6.6 years) was scored according to the Kellgren/Lawrence (K/L) grading system. Alignment was measured by the femorotibial angle on radiographs at baseline. Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA., Results: Of 2,664 knees, 1,012 (38%) were considered to have normal alignment, 693 (26%) had varus alignment, and 959 (36%) had valgus alignment. A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 0.97-2.44), and varus alignment was associated with a 2-fold increased risk (OR 2.06, 95% CI 1.28-3.32). Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non-overweight persons. The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment (OR 2.90, 95% CI 1.07-7.88)., Conclusion: An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA. However, this association seems particularly applicable to overweight and obese persons.

Objective: To provide an overview of prognostic factors of knee osteoarthritis (OA) progression., Methods: We searched Medline and Embase up to December 2003 according to a specified search strategy (keywords for disease, location, and study design). Studies that fulfilled predefined criteria were assessed for methodologic quality. Study characteristics and associations were extracted and the results were summarized according to a best evidence synthesis., Results: Of the 1,004 studies found, 37 met the inclusion criteria. Methodologic quality was assessed and only high-quality studies were included (n = 36). The best evidence synthesis yielded strong evidence that hyaluronic acid serum levels and generalized OA are predictive for progression of knee OA. Sex, knee pain, radiologic severity, knee injury, quadriceps strength, and regular sport activities were not predictive. Conflicting evidence for associations was found for several factors including body mass index and age. Limited evidence for an association with progression of knee OA was found for several factors, including the alignment (varus/valgus) of the joint. Limited evidence for no association with progression of OA was also found for several factors, including meniscectomy, several markers of bone or cartilage turnover, and the clinical diagnosis of localized OA., Conclusion: Generalized OA and level of hyaluronic acid seem to be associated with the radiologic progression of knee OA. Knee pain, radiologic severity at baseline, sex, quadriceps strength, knee injury, and regular sport activities seem not to be related. For other factors, the evidence was limited or conflicting.

Objective: To investigate the relationship between body mass index (BMI) and the incidence and progression of radiological knee as well as of radiological hip osteoarthritis., Design: Cohort study., Setting: Population based., Participants: 3585 people aged > or =55 years were selected from the Rotterdam Study, on the basis of the availability of radiographs of baseline and follow-up., Main Outcome Measures: Incidence of knee or hip osteoarthritis was defined as minimally grade 2 at follow-up and grade 0 or 1 at baseline. The progression of osteoarthritis was defined as a decrease in joint space width., Methods: x Rays of the knee and hip at baseline and follow-up (mean follow-up of 6.6 years) were evaluated. BMI was measured at baseline., Results: A high BMI (>27 kg/m(2)) at baseline was associated with incident knee osteoarthritis (odds ratio (OR) 3.3), but not with incident hip osteoarthritis. A high BMI was also associated with progression of knee osteoarthritis (OR 3.2). For the hip, a significant association between progression of osteoarthritis and BMI was not found., Conclusion: On the basis of these results, we conclude that BMI is associated with the incidence and progression of knee osteoarthritis. Furthermore, it seems that BMI is not associated with the incidence and progression of hip osteoarthritis.

Objective: To evaluate the risk of future hip or knee osteoarthritis (OA) in subjects with hand OA at baseline and to evaluate whether the concurrent presence of hand OA, other risk factors for OA, or an OA biomarker (type II collagen C-telopeptide degradation product [CTX-II]) further increases the risk., Methods: Radiographs of the hands (baseline) and the hips and knees (baseline and 6.6 years later) were obtained in a randomly selected subset of participants in the Rotterdam Study who were ages 55 years and older. Radiographs were scored for the presence of OA using the Kellgren/Lawrence (K/L) system. A total of 1,235 subjects without OA of the hip/knee (K/L score 0-1) at baseline were included in the study. CTX-II levels were measured at baseline. The independent risk of future hip/knee OA in subjects with hand OA at baseline was assessed by logistic regression, as stratified for age, sex, body mass index, family history of OA, and heavy workload., Results: Overall 12.1% of the participants (19.7% of those with hand OA versus 10.0% of those without) developed hip or knee OA (odds ratio [OR] 2.1 [95% confidence interval (95% CI) 1.3-3.1]). Subjects with hand OA had an increased risk of future hip OA (OR 3.0 [95% CI 1.6-5.4]), which was further increased in those with a family history of OA. Subjects with hand OA had an OR of 1.6 [95% CI 1.0-2.8) for the future development of knee OA, which was further increased in those who were overweight. Concurrent hand OA and high levels of CTX-II further increased the risk of having hip or knee OA at followup (OR 4.2 [95% CI 2.3-7.8])., Conclusion: The presence of hand OA at baseline showed an increased risk of future hip/knee OA (higher for hip OA than for knee OA). The concurrent presence of hand OA and other OA risk factors or high CTX-II levels further increased the risk of future hip/knee OA.

Objective: To investigate the influence of the use of various types of nonsteroidal antiinflammatory drugs (NSAIDs) on progression of osteoarthritis (OA) of the hip and knee., Methods: In 1,695 subjects (2,514 hips) and 635 subjects (874 knees) ages 55 years and older from the Rotterdam Study, radiographs of the hip and knee at baseline and followup (mean followup time 6.6 years) were evaluated. Radiologic OA (ROA) progression was defined as a minimum increase of 1 in the Kellgren/Lawrence grade or incident joint replacement at followup. The associations between the different types of NSAIDs and progression of ROA were assessed using multivariate logistic regression analysis., Results: Those subjects who were receiving diclofenac >180 days had a 2.4-fold increased risk (95% confidence interval [95% CI] 1.0-6.2) of progression of hip ROA and a 3.2-fold increased risk (95% CI 1.0-9.9) of knee ROA, compared with those considered short-term users (diclofenac for 1-30 days). These associations were adjusted for age, sex, body mass index, baseline ROA, followup time, and defined daily dosage., Conclusion: These data suggest that diclofenac may induce accelerated progression of hip and knee ROA. Whether this occurs because of a true deleterious effect on cartilage or because of excessive mechanical loading on a hip following pain relief remains to be investigated.